TP53-Induced Glycolysis and Apoptosis Regulator (TIGAR) Is Upregulated in Lymphocytes Stimulated with Concanavalin A.

The glycolytic modulator TP53-Inducible Glycolysis and Apoptosis Regulator (TIGAR) is overexpressed in several types of cancer and has a role in metabolic rewiring during tumor development. However, little is known about the role of this enzyme in proliferative tissues under physiological conditions. In the current work, we analysed the role of TIGAR in primary human lymphocytes stimulated with the mitotic agent Concanavalin A (ConA). We found that TIGAR expression was induced in stimulated lymphocytes through the PI3K/AKT pathway, since Akti-1/2 and LY294002 inhibitors prevented the upregulation of TIGAR in response to ConA. In addition, suppression of TIGAR expression by siRNA decreased the levels of the proliferative marker PCNA and increased cellular ROS levels. In this model, TIGAR was found to support the activity of glucose 6-phosphate dehydrogenase (G6PDH), the first enzyme of the pentose phosphate pathway (PPP), since the inhibition of TIGAR reduced G6PDH activity and increased autophagy. In conclusion, we demonstrate here that TIGAR is upregulated in stimulated human lymphocytes through the PI3K/AKT signaling pathway, which contributes to the redirection of the carbon flux to the PPP.

UnityMol prototype for FAIR sharing of molecular-visualization experiences: from pictures in the cloud to collaborative virtual reality exploration in immersive 3D environments.

Motivated by the current COVID-19 pandemic, which has spurred a substantial flow of structural data, the use of molecular-visualization experiences to make these data sets accessible to a broad audience is described. Using a variety of technology vectors related to the cloud, 3D and virtual reality gear, how to share curated visualizations of structural biology, modeling and/or bioinformatics data sets for interactive and collaborative exploration is examined. FAIR is discussed as an overarching principle for sharing such visualizations. Four initial example scenes related to recent COVID-19 structural data are provided, together with a ready-to-use (and share) implementation in the UnityMol software.

Physical, Modular and Articulated Interface for Interactive Molecular Manipulation.

Rational drug design is an approach based on detailed knowledge of molecular interactions and dynamic of bio-molecules. This approach involves designing new digital and interactive tools including classical desktop interaction devices as well as advanced ones such as haptic arms or virtual reality devices. These approaches however struggle to deal with flexibility of bio-molecules by simultaneously steering the numerous degrees of freedom. We propose a new method that follows a direct interaction approach by implementing an innovative methodology benefiting from a physical, modular and articulated molecular interface augmented by wireless embedded sensors. The goal is to create, design and steer its in silico twin virtual model and better interact with dynamic molecular models.

Overcoming the Heuristic Nature of k-Means Clustering: Identification and Characterization of Binding Modes from Simulations of Molecular Recognition Complexes.

The accurate and reproducible detection and description of thermodynamic states in computational data is a nontrivial problem, particularly when the number of states is unknown a priori and for large, flexible chemical systems and complexes. To this end, we report a novel clustering protocol that combines high-resolution structural representation, brute-force repeat clustering, and optimization of clustering statistics to reproducibly identify the number of clusters present in a data set (k) for simulated ensembles of butyrylcholinesterase in complex with two previously studied organophosphate inhibitors. Each structure within our simulated ensembles was depicted as a high-dimensionality vector with components defined by specific protein-inhibitor contacts at the chemical group level and the magnitudes of these components defined by their respective extents of pair-wise atomic contact, thus allowing for algorithmic differentiation between varying degrees of interaction. These surface-weighted interaction fingerprints were tabulated for each of over 1 million structures from more than 100 µs of all-atom molecular dynamics simulation per complex and used as the input for repetitive k-means clustering. Minimization of cluster population variance and range afforded accurate and reproducible identification of k, thereby allowing for the characterization of discrete binding modes from molecular simulation data in the form of contact tables that concisely encapsulate the observed intermolecular contact motifs. While the protocol presented herein to determine k and achieve non-heuristic clustering is demonstrated on data from massive atomistic simulation, our approach is generalizable to other data types and clustering algorithms, and is tractable with limited computational resources.

Visualizing protein structures - tools and trends.

Molecular visualization is fundamental in the current scientific literature, textbooks and dissemination materials. It provides an essential support for presenting results, reasoning on and formulating hypotheses related to molecular structure. Tools for visual exploration of structural data have become easily accessible on a broad variety of platforms thanks to advanced software tools that render a great service to the scientific community. These tools are often developed across disciplines bridging computer science, biology and chemistry. This mini-review was written as a short and compact overview for scientists who need to visualize protein structures and want to make an informed decision which tool they should use. Here, we first describe a few 'Swiss Army knives' geared towards protein visualization for everyday use with an existing large user base, then focus on more specialized tools for peculiar needs that are not yet as broadly known. Our selection is by no means exhaustive, but reflects a diverse snapshot of scenarios that we consider informative for the reader. We end with an account of future trends and perspectives.

Visualizing biomolecular electrostatics in virtual reality with UnityMol-APBS.

Virtual reality is a powerful tool with the ability to immerse a user within a completely external environment. This immersion is particularly useful when visualizing and analyzing interactions between small organic molecules, molecular inorganic complexes, and biomolecular systems such as redox proteins and enzymes. A common tool used in the biomedical community to analyze such interactions is the Adaptive Poisson-Boltzmann Solver (APBS) software, which was developed to solve the equations of continuum electrostatics for large biomolecular assemblages. Numerous applications exist for using APBS in the biomedical community including analysis of protein ligand interactions and APBS has enjoyed widespread adoption throughout the biomedical community. Currently, typical use of the full APBS toolset is completed via the command line followed by visualization using a variety of two-dimensional external molecular visualization software. This process has inherent limitations: visualization of three-dimensional objects using a two-dimensional interface masks important information within the depth component. Herein, we have developed a single application, UnityMol-APBS, that provides a dual experience where users can utilize the full range of the APBS toolset, without the use of a command line interface, by use of a simple graphical user interface (GUI) for either a standard desktop or immersive virtual reality experience.

Molecular Graphics: Bridging Structural Biologists and Computer Scientists.

Visualization of molecular structures is one of the most common tasks carried out by structural biologists, typically using software, such as Chimera, COOT, PyMOL, or VMD. In this Perspective article, we outline how past developments in computer graphics and data visualization have expanded the understanding of biomolecular function, and we summarize recent advances that promise to further transform structural biology. We also highlight how progress in molecular graphics has been impeded by communication barriers between two communities: the computer scientists driving these advances, and the structural and computational biologists who stand to benefit. By pointing to canonical papers and explaining technical progress underlying new graphical developments in simple terms, we aim to improve communication between these communities; this, in turn, would help shape future developments in molecular graphics.

Occurrence of salmonella spp. in broiler chicken feces in the central region of the state of Minas Gerais, Brazil

Bacteria of the genus Salmonella are gram-negative rods, facultative anaerobic non-spore formers, which may or may not be flagellated. These bacteria are frequently detected in poultry products and are important in animal and public health. The purpose of this study was to investigate the occurrence of Salmonella spp. in feces from broiler chicken litters located in municipalities of the central region of the state of Minas Gerais, Brazil. The study analyzed 845 feces samples from different poultry farms collected between September 2016 and March 2017. Pre-enrichment broths, specific selective broths and selective indicator agar were used for the analyses. The suspected isolates were submitted to biochemical testing and serotyping with "O" and "H" antisera to identify the Salmonella serotypes. The results showed that 213 feces samples were contaminated with Salmonella, and the serotypes found were: S. Minnesota, S. Sandiego, S. Schwarzengrund, S. Infantis, S. Hadar, S. enterica subsp. enterica (O: 4.5), S. Montevideo, S. Miami, S. Heidelberg, S. Cerro, S. Ndolo, S. Panama, S. Anatum, S. Tennessee, S. Agona, S. Newport and S. Muenster. The Minnesota serotype was predominant among the isolates investigated. Actions to improve the biosafety of commercial poultry farms are necessary to prevent possible contamination of poultry products that endanger human health.

As bactérias do gênero Salmonella são bastonetes gram-negativos, formadores anaeróbicos facultativos não esporos, que podem ou não ser flagelados. Essas bactérias são freqüentemente detectadas em produtos avícolas e são importantes na saúde animal e pública. O objetivo deste estudo foi investigar a ocorrência de Salmonella spp. em fezes de ninhadas de frangos de corte localizados em municípios da região central do estado de Minas Gerais, Brasil. O estudo analisou 845 amostras de fezes de diferentes granjas de aves coletadas entre setembro de 2016 e março de 2017. Caldos de pré-enriquecimento, caldos seletivos específicos e ágar indicador seletivo foram utilizados para as análises. Os isolados suspeitos foram submetidos a testes bioquímicos e sorotipagem com anti-soros "O" e "H" para identificar os sorotipos de Salmonella. Os resultados mostraram que 213 amostras de fezes estavam contaminadas com Salmonella, e os sorotipos encontrados foram: S. Minnesota, S. Sandiego, S. Schwarzengrund, S. Infantis, S. Hadar, S. enterica subsp. enterica (O: 4.5), S. Montevidéu, S. Miami, S. Heidelberg, S. Cerro, S. Ndolo, S. Panamá, S. Anatum, S. Tennessee, S. Agona, S. Newport e S. Muenster . O sorotipo Minnesota foi predominante entre os isolados investigados. Ações para melhorar a biossegurança das granjas comerciais de aves são necessárias para evitar a possível contaminação dos produtos avícolas que põem em risco a saúde humana.

MinOmics, an Integrative and Immersive Tool for Multi-Omics Analysis.

Proteomic and transcriptomic technologies resulted in massive biological datasets, their interpretation requiring sophisticated computational strategies. Efficient and intuitive real-time analysis remains challenging. We use proteomic data on 1417 proteins of the green microalga Chlamydomonas reinhardtii to investigate physicochemical parameters governing selectivity of three cysteine-based redox post translational modifications (PTM): glutathionylation (SSG), nitrosylation (SNO) and disulphide bonds (SS) reduced by thioredoxins. We aim to understand underlying molecular mechanisms and structural determinants through integration of redox proteome data from gene- to structural level. Our interactive visual analytics approach on an 8.3 m2 display wall of 25 MPixel resolution features stereoscopic three dimensions (3D) representation performed by UnityMol WebGL. Virtual reality headsets complement the range of usage configurations for fully immersive tasks. Our experiments confirm that fast access to a rich cross-linked database is necessary for immersive analysis of structural data. We emphasize the possibility to display complex data structures and relationships in 3D, intrinsic to molecular structure visualization, but less common for omics-network analysis. Our setup is powered by MinOmics, an integrated analysis pipeline and visualization framework dedicated to multi-omics analysis. MinOmics integrates data from various sources into a materialized physical repository. We evaluate its performance, a design criterion for the framework.

Emergence of Bordetella holmesii as a Causative Agent of Whooping Cough, Barcelona, Spain.

We describe the detection of Bordetella holmesii as a cause of whooping cough in Spain. Prevalence was 3.9% in 2015, doubling to 8.8% in 2016. This emergence raises concern regarding the contribution of B. holmesii to the reemergence of whooping cough and the effectiveness of the pertussis vaccine.

Right lateral versus left lateral view for forearm coronary angiography. An operator radiation exposure and image quality study.

OBJECTIVES: The aim of this study was to analyze the operator radiation exposure (ORE) and the image quality in a coronary angiography (CA) of the standard left lateral view (LLV) and compare it with an alternative right lateral view (RLV). BACKGROUND: Interventional cardiologists are exposed to high doses of scatter radiation, especially in angulated projections. METHODS: We prospectively included consecutive patients who underwent diagnostic CA. A standard +90° LLV and an alternative RLV (-90°) were done in each patient with the same protocol. The operator effective dose rate (mSv/h) was determined for each projection with digital dosimeters located in the collar, waist and knee. The image quality of both the LLV and RLV was analyzed and compared to a standard projection. RESULTS: 116 patients were enrolled; left coronary artery (LCA) was assessed in 52 patients and right coronary artery (RCA) in 64 patients. The ORE was significantly lower with the RLV compared to the conventional LLV with a maximum ORE reduction of 91.5% in the operator waist (LLV: 6.84 mSv h-1 versus RLV: 0.58 mSv h-1, p < 0.001). No significant differences in image quality were observed for the RCA in both projections. For the LCA, a slight loss of quality was observed with the RLV. CONCLUSIONS: -90° RLV is associated with a significant decrease in ORE compared to the conventional +90° LLV without losing image resolution for the RCA and resulting in a slight quality loss for the LCA evaluation. The RLV should be the first choice for RCA evaluation. For the LCA, the RLV loss of resolution should be balanced with the benefit of minimizing ORE, mainly in cases with long fluoroscopy times, such as complex percutaneous coronary interventional procedures.

Fermented milk containing Lactobacillus paracasei subsp. paracasei CNCM I-1518 reduces bacterial translocation in rats treated with carbon tetrachloride.

Probiotics can prevent pathological bacterial translocation by modulating intestinal microbiota and improving the gut barrier. The aim was to evaluate the effect of a fermented milk containing Lactobacillus paracasei subsp. paracasei CNCM I-1518 on bacterial translocation in rats with carbon tetrachloride (CCl4)-induced cirrhosis. Sprague-Dawley rats treated with CCl4 were randomized into a probiotic group that received fermented milk containing Lactobacillus paracasei subsp. paracasei CNCM I-1518 in drinking water or a water group that received water only. Laparotomy was performed one week after ascites development. We evaluated bacterial translocation, intestinal microbiota, the intestinal barrier and cytokines in mesenteric lymph nodes and serum. Bacterial translocation decreased and gut dysbiosis improved in the probiotic group compared to the water group. The ileal ß-defensin-1 concentration was higher and ileal malondialdehyde levels were lower in the probiotic group than in water group. There were no differences between groups in serum cytokines but TNF-α levels in mesenteric lymph nodes were lower in the probiotic group than in the water group. Fermented milk containing Lactobacillus paracasei subsp. paracasei CNCM I-1518 decreases bacterial translocation, gut dysbiosis and ileal oxidative damage and increases ileal ß-defensin-1 expression in rats treated with CCl4, suggesting an improvement in the intestinal barrier integrity.

A microbial signature for Crohn's disease.

OBJECTIVE: A decade of microbiome studies has linked IBD to an alteration in the gut microbial community of genetically predisposed subjects. However, existing profiles of gut microbiome dysbiosis in adult IBD patients are inconsistent among published studies, and did not allow the identification of microbial signatures for CD and UC. Here, we aimed to compare the faecal microbiome of CD with patients having UC and with non-IBD subjects in a longitudinal study. DESIGN: We analysed a cohort of 2045 non-IBD and IBD faecal samples from four countries (Spain, Belgium, the UK and Germany), applied a 16S rRNA sequencing approach and analysed a total dataset of 115 million sequences. RESULTS: In the Spanish cohort, dysbiosis was found significantly greater in patients with CD than with UC, as shown by a more reduced diversity, a less stable microbial community and eight microbial groups were proposed as a specific microbial signature for CD. Tested against the whole cohort, the signature achieved an overall sensitivity of 80% and a specificity of 94%, 94%, 89% and 91% for the detection of CD versus healthy controls, patients with anorexia, IBS and UC, respectively. CONCLUSIONS: Although UC and CD share many epidemiologic, immunologic, therapeutic and clinical features, our results showed that they are two distinct subtypes of IBD at the microbiome level. For the first time, we are proposing microbiomarkers to discriminate between CD and non-CD independently of geographical regions.

MetaTrans: an open-source pipeline for metatranscriptomics.

To date, meta-omic approaches use high-throughput sequencing technologies, which produce a huge amount of data, thus challenging modern computers. Here we present MetaTrans, an efficient open-source pipeline to analyze the structure and functions of active microbial communities using the power of multi-threading computers. The pipeline is designed to perform two types of RNA-Seq analyses: taxonomic and gene expression. It performs quality-control assessment, rRNA removal, maps reads against functional databases and also handles differential gene expression analysis. Its efficacy was validated by analyzing data from synthetic mock communities, data from a previous study and data generated from twelve human fecal samples. Compared to an existing web application server, MetaTrans shows more efficiency in terms of runtime (around 2 hours per million of transcripts) and presents adapted tools to compare gene expression levels. It has been tested with a human gut microbiome database but also proposes an option to use a general database in order to analyze other ecosystems. For the installation and use of the pipeline, we provide a detailed guide at the following website (www.metatrans.org).

Cobertura de vacunación antineumocócica en niños con condiciones de riesgo en Cataluña / Pneumococcal vaccination coverage in at-risk children in Catalonia

INTRODUCCIÓN: En Cataluña, el sistema público de sanidad solo financia la vacunación antineumocócica en pediatría a niños con condiciones de riesgo. El objetivo del estudio fue determinar la cobertura de dicha vacunación y su asociación con la edad, factores sociodemográficos y otras variables. MATERIAL Y MÉTODO: Estudio descriptivo transversal de los niños de 2 meses a 15 años de edad, asignados a los centros de atención primaria de Cataluña, y con enfermedades para las que el programa oficial de vacunas indica la vacunación antineumocócica. La información sobre el estado vacunal y las variables en estudio se recogió a partir de los datos registrados en la historia clínica electrónica de los equipos de atención primaria. Se analizó la asociación de la vacunación antineumocócica con variables demográficas y médicas mediante un análisis bivariado y un modelo de regresión logística múltiple, utilizando como medida de asociación la odds ratio ajustada (ORa), con su intervalo de confianza al 95%. RESULTADOS: La cobertura vacunal fue del 47,7%. Las variables asociadas a la vacunación fueron: edad (ORa: 9,2 [7,9-10,7] en niños de 2 meses a 2 años; ORa: 8,1 [7,0-9,3] en ni˜nos de 3-5 a˜nos; ORa: 4,6 [4,0-5,2] en niños de 6-11 años), nacionalidad española (ORa: 3,9 [3,5-4,3]), inmunización correcta según el calendario de vacunación sistemática (ORa: 2,5 [2,1-3,0]), y número de condiciones de riesgo (ORa: 3,2 [2,5-4,1] en niños con 2 o más condiciones). CONCLUSIONES: La cobertura vacunal frente a neumococo en niños con condiciones de riesgo es baja en Cataluña. Es necesario implementar estrategias para aumentar la cobertura

INTRODUCTION: The public health system in Catalonia only funds pneumococcal vaccination in paediatrics for children at-risk. The aim of this study was to determine pneumococcal vaccination coverage and its association with age, sociodemographic factors and other variables. MATERIAL AND METHOD: Descriptive cross-sectional study of children aged between 2 months and 15 years old assigned to primary care centres in Catalonia and with diseases that are included for pneumococcal vaccine in the official vaccination program. The information on vaccination status and study variables were obtained from data registered in the electronic medical records in the primary care centres. An analysis was made of the association between pneumococcal vaccination and demographic and medical variables using bivariate analysis and a multiple logistic regression model. The adjusted odds ratio (aOR), with a confidence interval of 95%, was used to measure the relationships. RESULTS: Pneumococcal vaccination coverage was 47.7%. Variables which predicted pneumococcal vaccination were: age (aOR: 9.2 [7.9-10.7] in children 2 months-2 years old; aOR 8.1 [7.0-9.3] in children 3-5 years; aOR: 4.6 [4.0-5.2] in children 6-10 years), Spanish nationality (aOR: 3.9 [3.5-4.3]), correct immunisation according to systematic immunisation schedule (aOR: 2.5 [2.1-3.0]), and number of risk conditions (aOR: 3.2 [2.5-4.1] in children with 2 or more conditions). CONCLUSIONS: Pneumococcal vaccination coverage in children with risk conditions is low in Catalonia. Strategies need to be implemented to increase coverage

[Pneumococcal vaccination coverage in at-risk children in Catalonia]. / Cobertura de vacunación antineumocócica en niños con condiciones de riesgo en Cataluña.

INTRODUCTION: The public health system in Catalonia only funds pneumococcal vaccination in paediatrics for children at-risk. The aim of this study was to determine pneumococcal vaccination coverage and its association with age, sociodemographic factors and other variables. MATERIAL AND METHOD: Descriptive cross-sectional study of children aged between 2 months and 15 years old assigned to primary care centres in Catalonia and with diseases that are included for pneumococcal vaccine in the official vaccination program. The information on vaccination status and study variables were obtained from data registered in the electronic medical records in the primary care centres. An analysis was made of the association between pneumococcal vaccination and demographic and medical variables using bivariate analysis and a multiple logistic regression model. The adjusted odds ratio (aOR), with a confidence interval of 95%, was used to measure the relationships. RESULTS: Pneumococcal vaccination coverage was 47.7%. Variables which predicted pneumococcal vaccination were: age (aOR: 9.2 [7.9-10.7] in children 2 months-2 years old; aOR 8.1 [7.0-9.3] in children 3-5 years; aOR: 4.6 [4.0-5.2] in children 6-10 years), Spanish nationality (aOR: 3.9 [3.5-4.3]), correct immunisation according to systematic immunisation schedule (aOR: 2.5 [2.1-3.0]), and number of risk conditions (aOR: 3.2 [2.5-4.1] in children with 2 or more conditions). CONCLUSIONS: Pneumococcal vaccination coverage in children with risk conditions is low in Catalonia. Strategies need to be implemented to increase coverage.

Processing faecal samples: a step forward for standards in microbial community analysis.

BACKGROUND: The microbial community analysis of stools requires optimised and standardised protocols for their collection, homogenisation, microbial disruption and nucleic acid extraction. Here we examined whether different layers of the stool are equally representative of the microbiome. We also studied the effect of stool water content, which typically increases in diarrhoeic samples, and of a microbial disruption method on DNA integrity and, therefore, on providing an unbiased microbial composition analysis. RESULTS: We collected faecal samples from healthy subjects and performed microbial composition analysis by pyrosequencing the V4 region of the 16S rRNA gene. To examine the effect of stool structure, we compared the inner and outer layers of the samples (N = 8). Both layers presented minor differences in microbial composition and abundance at the species level. These differences did not significantly bias the microbial community specific to an individual. To evaluate the effect of stool water content and bead-beating, we used various volumes of a water-based salt solution and beads of distinct weights before nucleic acid extraction (N = 4). The different proportions of water did not affect the UniFrac-based clustering of samples from the same subject However, the use or omission of a bead-beating step produced different proportions of Gram-positive and Gram-negative bacteria and significant changes in the UniFrac-based clustering of the samples. CONCLUSION: The degree of hydration and homogenisation of faecal samples do not significantly alter their microbial community composition. However, the use of bead-beating is critical for the proper detection of Gram-positive bacteria such as Blautia and Bifidobacterium.

Vaccination of patients with inflammatory bowel disease. Practical recommendations.

Patients with inflammatory bowel disease (IBD) have a greater risk of infection associated with the endogenous immunosuppression brought about by their underlying disease as well as the exogenous immunosuppression resulting from their therapies. In the last few years guidelines and consensus papers have been issued on the indication of vaccines for these patients as primary prevention of infection. However, vaccine coverage is low, likely because the risk for infection and both safety and efficacy concerns regarding vaccines are scarcely perceived in such cases. The available scientific evidence shows that immunization is safe for most preparations, and bears no association with an increased risk for disease activity. This paper reviews the available scientific literature, and provides recommendations on the vaccination of adults with IBD.

Vacunación de pacientes con enfermedad inflamatoria intestinal. Recomendaciones prácticas / Vaccination of patients with inflammatory bowel disease. Practical recommendations

Los pacientes con enfermedad inflamatoria intestinal (EII) tienen un mayor riesgo de infecciones, asociado tanto a la inmunosupresión endógena condicionada por su enfermedad de base, como a la exógena generada por los tratamientos que reciben. En los últimos años se han publicado guías y documentos de consenso sobre indicaciones de vacunación en estos pacientes, como medida de prevención primaria de infecciones. Sin embargo, las coberturas vacunales alcanzadas son bajas, probablemente por la falta de percepción del riesgo de infección y las dudas sobre la seguridad y eficacia de las vacunas en estos casos. La evidencia científica disponible muestra que la inmunización es segura para la mayoría de preparados y no se asocia a un incremento del riesgo de actividad de la enfermedad. En este documento se revisa la literatura científica disponible y se presentan unas recomendaciones de vacunación para pacientes adultos con EII(AU)

Patients with inflammatory bowel disease (IBD) have a greater risk of infection associated with the endogenous immunosuppression brought about by their underlying disease as well as the exogenous immunosuppression resulting from their therapies. In the last few years guidelines and consensus papers have been issued on the indication of vaccines for these patients as primary prevention of infection. However, vaccine coverage is low, likely because the risk for infection and both safety and efficacy concerns regarding vaccines are scarcely perceived in such cases. The available scientific evidence shows that immunization is safe for most preparations, and bears no association with an increased risk for disease activity. This paper reviews the available scientific literature, and provides recommendations on the vaccination of adults with IBD(AU)